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Frontiers in Immunology 2023High-mobility group box 1 (HMGB1) is a non-histone nuclear protein and can be extracellularly secreted to induce sterile inflammation. Although uterine deletion of HMGB1...
INTRODUCTION
High-mobility group box 1 (HMGB1) is a non-histone nuclear protein and can be extracellularly secreted to induce sterile inflammation. Although uterine deletion of HMGB1 causes implantation and decidualization defects, how secreted HMGB1 is involved in mouse early pregnancy is still unknown.
METHODS
Mouse models, mouse primary endometrial cells and human endometrial cell lines were used in this study. Both immunofluorescence and Western blot were performed to show the localization and relative level of HMGB1 and acetylated HMGB1, respectively. Relative mRNA levels were analyzed by real time RT-PCR.
RESULTS
The secreted HMGB1 was detected in uterine lumen fluid in mouse periimplantation uterus. There is an obvious difference for secreted HMGB1 levels in uterine fluid between day 4 of pregnancy and day 4 of pseudopregnancy, suggesting the involvement of blastocysts during HMGB1 secretion. Trypsin is clearly detected in mouse blastocyst cavity and in the supernatant of cultured blastocysts. Trypsin significantly stimulates HB-EGF production through activating PAR2 and ADAM17. Uterine injection of PAR2 inhibitor into day 4 pregnant mice significantly reduces the number of implantation sites. HB-EGF released from luminal epithelium can induce mouse in vitro decidualization. The conditioned medium collected from trypsin-treated luminal epithelium is able to induce in vitro decidualization, which is suppressed by EGFR inhibitor. Intrauterine injection of glycyrrhizin (HMGB1 inhibitor) can significantly inhibit mouse embryo implantation. We also showed that exogenous HMGB1 released from human epithelial cells are able to induce human in vitro decidualization.
CONCLUSION
Trypsin can induce decidualization of stromal cells via PAR2-HMGB1-ADAM17-HB-EGF from luminal epithelium.
Topics: Pregnancy; Female; Mice; Animals; Humans; Heparin-binding EGF-like Growth Factor; Trypsin; HMGB1 Protein; Embryo Implantation; Uterus
PubMed: 36761729
DOI: 10.3389/fimmu.2023.1024706 -
Animal Science Journal = Nihon Chikusan... 2023This study was conducted to examine the effects of different pseudopregnancy periods in nonpregnant sows on artificial lactation induction efficiency and milk...
This study was conducted to examine the effects of different pseudopregnancy periods in nonpregnant sows on artificial lactation induction efficiency and milk composition. Sixteen pseudopregnant sows (n = 4 per group) were treated with 5 mg of estradiol dipropionate at 28 (Group D38), 35 (Group D45), 42 (Group D52), and 49 (Group D59) days after the end of estrus, followed by prostaglandin F as 0.175-mg cloprostenol twice at 12 h intervals 10 days later. The overall success rate of lactation induction was 81.3%. The lactation rates were significantly higher in Groups D38, D45, and D59 (100.0%) than in Group D52 (25.0%). The milk immunoglobulin (Ig) G concentration was significantly higher in Group D38 than in Group D59. However, IgA levels and milk compositions (protein, ash, and lactose) did not differ among the groups. Lactation induction was successful between 38 and 59 days of pseudopregnancy. Apart from IgG, pseudopregnancy length did not affect milk components from 38 to 59 days of pseudopregnancy.
Topics: Pregnancy; Swine; Animals; Female; Pseudopregnancy; Estrus; Prostaglandins F; Milk; Lactation
PubMed: 36752079
DOI: 10.1111/asj.13815 -
Hormones and Behavior Mar 2023In placental mammals, estradiol levels are chronically elevated during pregnancy, but quickly drop to prepartum levels following birth. This may produce an "estrogen...
Estradiol withdrawal following a hormone simulated pregnancy induces deficits in affective behaviors and increases ∆FosB in D1 and D2 neurons in the nucleus accumbens core in mice.
In placental mammals, estradiol levels are chronically elevated during pregnancy, but quickly drop to prepartum levels following birth. This may produce an "estrogen withdrawal" state that has been linked to changes in affective states in humans and rodents during the postpartum period. The neural mechanisms underlying these affective changes, however, are understudied. We used a hormone-simulated pseudopregnancy (HSP), a model of postpartum estrogen withdrawal, in adult female C57BL/6 mice to test the impact of postpartum estradiol withdrawal on several behavioral measures of anxiety and motivation. We found that estradiol withdrawal following HSP increased anxiety-like behavior in the elevated plus maze, but not in the open field or marble burying tests. Although hormone treatment during HSP consistently increased sucrose consumption, sucrose preference was generally not impacted by hormone treatment or subsequent estradiol withdrawal. In the social motivation test, estradiol withdrawal decreased the amount of time spent in proximity to a social stimulus animal. These behavioral changes were accompanied by changes in the expression of ∆FosB, a transcription factor correlated with stable long-term plasticity, in the nucleus accumbens (NAc). Specifically, estrogen-withdrawn females had higher ∆FosB expression in the nucleus accumbens core, but ∆FosB expression did not vary across hormone conditions in the nucleus accumbens shell. Using transgenic reporter mice, we found that this increase in ∆FosB occurred in both D1- and D2-expressing cells in the NAc core. Together, these results suggest that postpartum estrogen withdrawal impacts anxiety and motivation and increases ∆FosB in the NAc core.
Topics: Animals; Female; Mice; Pregnancy; Estradiol; Estrogens; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Nucleus Accumbens; Placenta; Receptors, Dopamine D1; Sucrose
PubMed: 36645923
DOI: 10.1016/j.yhbeh.2023.105312 -
Neuroscience and Biobehavioral Reviews Feb 2023Placentophagia, ingestion of placenta and amniotic fluid, usually during parturition, is a behavioral feature of nearly all nonaquatic, placental mammals, and is a nexus... (Review)
Review
Placentophagia, ingestion of placenta and amniotic fluid, usually during parturition, is a behavioral feature of nearly all nonaquatic, placental mammals, and is a nexus for several interlocking behavioral phenomena. Placentophagia has not been typical of human cultures, but in recent years, some women in affluent societies have engaged in it, thereby bringing publicity to the behavior. First, we summarized benefits of placentophagia for nonhuman mammals, which include increased attractiveness of neonates, enhanced onset of maternal behavior, suppression of pseudopregnancy, and enhancement of opioid hypoalgesia by Placental Opioid-Enhancing Factor (POEF), a benefit that may extend well outside the context of parturition. The research on POEF in animals was discussed in detail. Then we discussed placentophagia (placentophagy) in humans, and whether there is validity to the claims of various benefits reported primarily in the pro-placentophagy literature, and, although human afterbirth shows POEF activity, the POEF effect has not yet been tested in humans. Finally, we discussed the general possible implications, for the management of pain and addiction, of isolating and characterizing POEF.
Topics: Animals; Infant, Newborn; Female; Pregnancy; Humans; Analgesics, Opioid; Placenta; Postpartum Period; Pain; Maternal Behavior; Mammals
PubMed: 36509207
DOI: 10.1016/j.neubiorev.2022.104992 -
Industrial Psychiatry Journal 2022Delusional disorders are common psychiatric disorders, but a delusion of pregnancy is a rare condition. Four cases that presented at a single tertiary care psychiatry...
Delusional disorders are common psychiatric disorders, but a delusion of pregnancy is a rare condition. Four cases that presented at a single tertiary care psychiatry center with delusion of pregnancy as a part of different psychological disorders are illustrated here. These cases were seen over a period of 6 months and had varied presentations and associated psychopathologies. Three of the four patients showed rapid recovery to treatment, but one patient was lost to follow-up. The heterogeneity in the presentation, sociodemographic profile of the patients and even in the symptom profile and response to treatment in this condition is highlighted and discussed in this case series.
PubMed: 36419711
DOI: 10.4103/ipj.ipj_166_21 -
Scientific Reports Oct 2022The rodent estrous cycle modulates a range of biological functions, from gene expression to behavior. The cycle is typically divided into four stages, each characterized...
The rodent estrous cycle modulates a range of biological functions, from gene expression to behavior. The cycle is typically divided into four stages, each characterized by distinct hormone concentration profiles. Given the difficulty of repeatedly sampling plasma steroid hormones from rodents, the primary method for classifying estrous stage is by identifying vaginal epithelial cell types. However, manual classification of epithelial cell samples is time-intensive and variable, even amongst expert investigators. Here, we use a deep learning approach to achieve classification accuracy at expert level. Due to the heterogeneity and breadth of our input dataset, our deep learning approach ("EstrousNet") is highly generalizable across rodent species, stains, and subjects. The EstrousNet algorithm exploits the temporal dimension of the hormonal cycle by fitting classifications to an archetypal cycle, highlighting possible misclassifications and flagging anestrus phases (e.g., pseudopregnancy). EstrousNet allows for rapid estrous cycle staging, improving the ability of investigators to consider endocrine state in their rodent studies.
Topics: Female; Animals; Rodentia; Deep Learning; Estrus; Estrous Cycle; Hormones
PubMed: 36271290
DOI: 10.1038/s41598-022-22392-w -
The Journal of Reproduction and... Oct 2022The present study established techniques to induce pseudopregnancy, in vitro oocyte cultures from pronuclear to 2- to 4-cell stages, and embryo transfer in musk shrews,...
The present study established techniques to induce pseudopregnancy, in vitro oocyte cultures from pronuclear to 2- to 4-cell stages, and embryo transfer in musk shrews, a reflex ovulator. Offspring were subsequently obtained by transferring in vivo-developed or in vitro-cultured embryos. Female musk shrews received human chronic gonadotropin (hCG), with or without mating stimuli, from vasectomized males to produce pseudopregnant recipients. Embryos at the 2- to 4-cell stage were collected 44-48 h after mating. Another set of embryos was collected 26-27 h after mating and then cultured for 20 h from the pronuclear to 2- to 4-cell stages. Subsequently, embryos were transferred into the oviducts of pseudopregnant recipients 24 or 48 h after the induction of pseudopregnancy. Offsprings were successfully obtained from recipients that received hCG 24 h before embryo transfer, regardless of mating stimuli. These techniques may be valuable for producing transgenic musk shrews.
Topics: Animals; Embryo Transfer; Female; Gonadotropins; Humans; Male; Oocytes; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic; Shrews
PubMed: 36070889
DOI: 10.1262/jrd.2022-003 -
Reproduction in Domestic Animals =... Dec 2022Anti-Müllerian hormone (AMH), known for its role during foetal sexual differentiation, is secreted by the Sertoli cells in males and the granulosa cells in females...
Anti-Müllerian hormone (AMH), known for its role during foetal sexual differentiation, is secreted by the Sertoli cells in males and the granulosa cells in females during post-natal life. As serum AMH concentrations correlate with follicle numbers, AMH is utilized as a marker of ovarian reserve in many species. In dogs and cats, AMH is used as a diagnostic tool to determine spay or neuter status. In the available literature, no research regarding serum AMH levels in rabbits has been published yet. The objectives of the present study were to (1) measure serum AMH concentrations in female rabbits and investigate the value of AMH as a diagnostic tool to differentiate between spayed and intact does and (2) relate measured AMH levels to pseudopregnancy and ovarian follicle numbers. For AMH measurement, serum samples were obtained from sexually intact (n = 64) and spayed (n = 22) female rabbits. Spayed does were of various breeds; intact rabbits were Zika hybrid rabbits. In the intact does, AMH measurement was complemented by determination of progesterone levels, gynaecological examination and histopathological evaluation of the uterus and ovaries, including follicle counts. Serum AMH and progesterone concentrations were measured using a human-based chemiluminescence immunoassay (CLIA) and an enzyme-linked fluorescence assay (ELFA), respectively. Depending on progesterone levels, sexually intact does were classified into follicular (n = 52) or luteal phase (n = 12). Median serum AMH levels were 1.53 ng/ml (range 0.77-3.36 ng/ml) in intact and 0.06 ng/ml (range ≤0.01-0.23 ng/ml) in spayed does. AMH concentrations between the intact and spayed rabbits differed significantly and did not overlap (p < .001). Receiver operating characteristic (ROC) curve analysis yielded a sensitivity and specificity of 100% for a cut-off level of 0.50 ng/ml. Follicular or luteal phase had no significant influence on measured AMH levels (t = 0.061, df = 62, p = .951). While the number of secondary follicles correlated significantly with AMH concentrations (r = 0.410, p = .001), the number of primary or antral follicles did not (r = 0.241, p = .055 and r = 0.137, p = .281, respectively). In conclusion, a single determination of serum AMH concentrations was adequate to distinguish spayed from intact female rabbits. Among sexually intact individuals, whether does were in follicular or luteal phase had no significant influence on measured serum AMH concentrations. The relationship between small growing follicles and AMH levels as described in other species could be partially confirmed, as secondary follicles correlated significantly with AMH.
Topics: Animals; Female; Male; Pregnancy; Rabbits; Anti-Mullerian Hormone; Ovarian Follicle; Progesterone; Pseudopregnancy
PubMed: 36052807
DOI: 10.1111/rda.14240 -
Metabolic Brain Disease Dec 2022Approximately 40% of women with epilepsy experience perimenstrual seizure exacerbation, referred to as catamenial epilepsy. These seizures result from cyclic changes in...
Approximately 40% of women with epilepsy experience perimenstrual seizure exacerbation, referred to as catamenial epilepsy. These seizures result from cyclic changes in circulating progesterone and estradiol levels and there is no effective treatment for this form of intractable epilepsy. We artificially increased progesterone levels and neurosteroid levels (pseudo-pregnancy) in adult Swiss albino female mice (19-23 g) by injecting them with pregnant mares' serum gonadotropin (5 IU s.c.), followed by human chorionic gonadotropin (5 IU s.c.) after 46 h. After this, ferulic acid (25, 50, 100 mg/kg i.p.) treatment was given for 10 days. During treatment, progesterone, estradiol, and corticosterone levels were estimated in blood on days 1, 5, and 10. Neurosteroid withdrawal was induced by finasteride (50 mg/kg, i.p.) on treatment day 9. Twenty-four hours after finasteride administration (day 10 of treatment), seizure susceptibility was evaluated with the sub-convulsant pentylenetetrazol (PTZ) dose (40 mg/kg i.p.). Four to six hours after PTZ, animals were assessed for depression like phenotypes using tail-suspension test (TST). Four to six hours following TST, animals were euthanized, and discrete brain parts (cortex and hippocampus) were separated for estimation of norepinephrine, serotonin, and dopamine as well as glutamic acid decarboxylase (GAD) enzyme activity. PMSG and HCG treatment elevated progesterone and estradiol levels, assessed on days 1, 5, and 10 causing a state of pseudo-pregnancy. Treatment with finasteride increased seizure susceptibility and depression-like characteristics possibly due to decreased progesterone and elevated estrogen levels coupled with decreased monoamine and elevated corticosterone levels. Ferulic acid treatment, on the other hand, significantly decreased seizure susceptibility and depression like behavior, possibly because of increased progesterone, restored estradiol, corticosterone, monoamines, and GAD enzyme activity. We concluded anticonvulsant effect of ferulic acid in a mouse model of catamenial epilepsy, evidenced by favourable seizure attenuation and curative effect on the circulating progesterone, estradiol, and corticosterone levels along with restorative effect on GAD enzyme activity and monoamine levels.
Topics: Adult; Female; Animals; Horses; Mice; Humans; Progesterone; Finasteride; Neurosteroids; Corticosterone; Epilepsy; Pentylenetetrazole; Seizures; Estradiol
PubMed: 35932441
DOI: 10.1007/s11011-022-01054-w -
Life (Basel, Switzerland) May 2022Reliable pregnancy diagnostics would be beneficial for monitoring polar bear () populations both in situ and ex situ, but currently there is no method of non-invasive...
Reliable pregnancy diagnostics would be beneficial for monitoring polar bear () populations both in situ and ex situ, but currently there is no method of non-invasive pregnancy detection in this species. Recent reports in several carnivore species described the identification of fecal proteins that may serve as pregnancy biomarkers; however, repeatability has been limited. The objective of the current analysis was to utilize an unbiased, antibody-free, label-free method for the identification and quantification of fecal proteins to determine if differences associated with pregnancy are detectable in polar bears. Protein was extracted from fecal samples ( = 48) obtained from parturient ( = 6) and non-parturient ( = 6) profiles each at four timepoints: pre-breeding season, embryonic diapause, early placental pregnancy, and mid-placental pregnancy. Protein was prepared and analyzed on the Thermo Orbitrap Eclipse nanoLC-MS/MS system. A total of 312 proteins was identified and quantified; however, coefficients of variation (CV) were high for both abundance ratio variability (384.8 ± 61.0% SEM) and within group variability (86.8 ± 1.5%). Results of this study suggest that the inconsistencies in specific protein concentrations revealed previously by antibody-based assays may not be due to that methodology's limitations, but rather, are reflective of true variation that exists among samples.
PubMed: 35743827
DOI: 10.3390/life12060796